Oxygen Sensing with Perfluorocarbon-Loaded Ultraporous Mesostructured Silica Nanoparticles.

Oxygen homeostasis is important in the regulation of biological function. Disease progression can be monitored by measuring oxygen levels, thus producing information for the design of therapeutic treatments. Noninvasive measurements of tissue oxygenation require the development of tools with minimal adverse effects and facile detection of features of interest. Fluorine magnetic resonance imaging (19F MRI) exploits the intrinsic properties of perfluorocarbon (PFC) liquids for anatomical imaging, cell tracking, and oxygen sensing. However, the highly hydrophobic and lipophobic properties of perfluorocarbons require the formation of emulsions for biological studies, though stabilizing these emulsions has been challenging. To enhance the stability and biological loading of perfluorocarbons, one option is to incorporate perfluorocarbon liquids into the internal space of biocompatible mesoporous silica nanoparticles. Here, we developed perfluorocarbon-loaded ultraporous mesostructured silica nanoparticles (PERFUMNs) as 19F MRI detectable oxygen-sensing probes. Ultraporous mesostructured silica nanoparticles (UMNs) have large internal cavities (average = 1.8 cm3 g-1), facilitating an average 17% loading efficiency of PFCs, meeting the threshold fluorine concentrations needed for imaging studies. Perfluoro-15-crown-5-ether PERFUMNs have the highest equivalent nuclei per PFC molecule and a spin-lattice (T1) relaxation-based oxygen sensitivity of 0.0032 mmHg-1 s-1 at 16.4 T. The option of loading PFCs after synthesizing UMNs, rather than traditional in situ core-shell syntheses, allows for use of a broad range of PFC liquids from a single material. The biocompatible and tunable chemistry of UMNs combined with the intrinsic properties of PFCs makes PERFUMNs a MRI sensor with potential for anatomical imaging, cell tracking, and metabolic spectroscopy with improved stability.

Effects of Mesoporous Silica Coating and Post-Synthetic Treatment on the Transverse Relaxivity of Iron Oxide Nanoparticles.

Mesoporous silica nanoparticles have the capacity to load and deliver therapeutic cargo and incorporate imaging modalities, making them prominent candidates for theranostic devices. One of the most widespread imaging agents utilized in this and other theranostic platforms is nanoscale superparamagnetic iron oxide. Although several core-shell magnetic mesoporous silica nanoparticles presented in the literature have provided high T2 contrast in vitro and in vivo, there is ambiguity surrounding which parameters lead to enhanced contrast. Additionally, there is a need to understand the behavior of these imaging agents over time in biologically relevant environments. Herein, we present a systematic analysis of how the transverse relaxivity (r2) of magnetic mesoporous silica nanoparticles is influenced by nanoparticle diameter, iron oxide nanoparticle core synthesis, and the use of a hydrothermal treatment. This work demonstrates that samples which did not undergo a hydrothermal treatment experienced a drop in r2 (75% of original r2 within 8 days of water storage), while samples with hydrothermal treatment maintained roughly the same r2 for over 30 days in water. Our results suggest that iron oxide oxidation is the cause of the r2 loss, and this oxidation can be prevented both during synthesis and storage by the use of deoxygenated conditions during nanoparticle synthesis. The hydrothermal treatment also provides colloidal stability, even in acidic and highly salted solutions, and a resistance against acid degradation of the iron oxide nanoparticle core. The results of this study show the promise of multifunctional mesoporous silica nanoparticles but will also likely inspire further investigation into multiples types of theranostic devices, taking into consideration their behavior over time and in relevant biological environments.